ABSTRACT
Immune checkpoint inhibitors (ICIs) including PD-1/PD-L1 antibodies, have demonstrated significant clinical benefits in the treatment of individuals with many types of cancer. However, as more and more patients use such therapies, the side effects of immune checkpoint inhibitors have also been discovered. These include accelerated tumor growth in some patients, creating new lesions, and even life-threatening ones. These side effects are known as hyperprogression disease (HPD), and different types of tumors have different HPD conditions after ICIs treatment. Therefore, understanding the pathogenesis of HPD and predicting its occurrence is critical for patients using ICIs therapy. Here, we will briefly review the current status of PD-1/PD-L1 antibody therapy, HPD occurrence in various types of tumors, and the underlying mechanism.
ABSTRACT
Background: EMILIN2 is a platelet-associated elastin that regulates angiogenesis. It has recently been found to play an essential role in various tumors. Nevertheless, the mechanism of action of EMILIN2 in clear cell renal cell carcinoma (ccRCC) remains unclear. Methods: Samples from 33 cancers were obtained from UCSC Xena and The Cancer Genome Atlas (TCGA) database. The relationship between EMILIN2 expression and the clinicopathological characteristics and immune infiltration of ccRCC was investigated. Nonnegative matrix factorization (NMF) was used to classify ccRCC patients. A multigene risk prediction model of ccRCC was constructed using LASSO regression and multivariate regression analysis. A nomogram survival probability prediction map and calibration curve were constructed based on clinical information. Results: EMILIN2 is significantly overexpressed in ccRCC, a phenomenon that is associated with poor prognosis. Meanwhile, EMILIN2 expression is closely related to tumor immune infiltration in ccRCC. Patients with clear cell renal cell carcinoma were divided into two subtypes using NMF, with subtype 2 showed poor prognosis. Next, we established a risk score model for ccRCC based on the common differentially expressed genes (DEGs) between subtypes and groups based on EMILIN2 expression. The results indicated poor prognosis in the high-risk group in the training set and were confirmed in the validation set. Conclusion: Our findings suggest that EMILIN2 expression is closely associated with immune infiltration in ccRCC. EMILIN2 expression is negatively correlated with the prognosis of ccRCC patients. Here, we developed a tool that could predict the prognosis of ccRCC patients.
ABSTRACT
Cyclic GMP-AMP synthase (cGAS) senses foreign DNA to produce 2'3'-cyclic GMP-AMP (2'3'-cGAMP). 2'3'-cGAMP is a second messenger that binds and activates the adaptor protein STING, which triggers the innate immune response. As a STING agonist, the small molecule 2'3'-cGAMP plays pivotal roles in antiviral defense and has adjuvant applications, and anti-tumor effects. 2'3'-cGAMP and its analogs are thus putative targets for immunotherapy and are currently being testedin clinical trials to treat solid tumors. However, several barriers to further development have emerged from these studies, such as evidence of immune and inflammatory side-effects, poor pharmacokinetics, and undesirable biodistribution. Here, we review the status of 2'3'-cGAMP research and outline the role of 2'3'-cGAMP in immune signaling, adjuvant applications, and cancer immunotherapy, as well as various 2'3'-cGAMP detection methods.
Subject(s)
Neoplasms , Nucleotides, Cyclic , Humans , Immunity, Innate , Neoplasms/drug therapy , Nucleotides, Cyclic/metabolism , Second Messenger Systems , Tissue DistributionABSTRACT
Electrospun micro/nanofibrous membranes (EFMs) have been widely investigated as local drug delivery systems. Multiple drugs can be simultaneously incorporated into one EFM to create synergistic effects, reduce side effects, and play their respective roles in the complex physiological processes of tissue regeneration and postoperative adhesion prevention. Due to the versatile electrospinning techniques, sustained and programmed release behaviors of multiple drugs could be achieved by modulating the structure of the EFMs and the location of the drugs. In this review, various multidrug incorporation approaches based on electrospinning are overviewed. In particular, the advantages and limitations of each drug incorporation technique, the methods to control drug release and the effect of one drug release on another are discussed. Then the applications of multidrug-loaded EFMs in regenerative medicine, including wound healing, bone regeneration, vascular tissue engineering, nerve regeneration, periodontal regeneration and adhesion prevention are comprehensively reviewed. Finally, the future perspectives and challenges in the research of multidrug-loaded EFMs are discussed.
